3-2871015-C-T

Variant names:

• chr3-2871015-C-T
• rs4234555
• NM_175607.3:c.652+4066C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175607.3(CNTN4):​c.652+4066C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.914 in 152,144 control chromosomes in the GnomAD database, including 63,666 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.91 (63666 hom., cov: 30)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175
• Publications: 1 publications found

Genes affected

CNTN4 (HGNC:2174): (contactin 4) This gene encodes a member of the contactin family of immunoglobulins. Contactins are axon-associated cell adhesion molecules that function in neuronal network formation and plasticity. The encoded protein is a glycosylphosphatidylinositol-anchored neuronal membrane protein that may play a role in the formation of axon connections in the developing nervous system. Deletion or mutation of this gene may play a role in 3p deletion syndrome and autism spectrum disorders. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2011]

CNTN4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• autism spectrum disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.652+4066C>T		intron_variant	Intron 8 of 24	ENST00000418658.6	NP_783200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6	c.652+4066C>T		intron_variant	Intron 8 of 24	5	NM_175607.3	ENSP00000396010.1

Frequencies

GnomAD3 genomes AF: 0.914 AC: 138977 AN: 152026 Hom.: 63618 Cov.: 30

Gnomad AFR AF: 0.953

Gnomad AMI AF: 0.857

Gnomad AMR AF: 0.942

Gnomad ASJ AF: 0.928

Gnomad EAS AF: 0.974

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.934

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.914 AC: 139081 AN: 152144 Hom.: 63666 Cov.: 30 AF XY: 0.914 AC XY: 67955 AN XY: 74344

African (AFR) AF: 0.953 AC: 39561 AN: 41520

American (AMR) AF: 0.942 AC: 14400 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.928 AC: 3221 AN: 3470

East Asian (EAS) AF: 0.974 AC: 5025 AN: 5160

South Asian (SAS) AF: 0.864 AC: 4165 AN: 4818

European-Finnish (FIN) AF: 0.881 AC: 9316 AN: 10578

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.888 AC: 60370 AN: 67996

Other (OTH) AF: 0.935 AC: 1973 AN: 2110

Alfa AF: 0.900 Hom.: 175718

Bravo AF: 0.922

Asia WGS AF: 0.924 AC: 3213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.77
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4234555; hg19: chr3-2912699;